Publications by authors named "Young In Park"

55 Publications

Adjuvanticity of Processed gel for Influenza Vaccination in Mice.

Immune Netw 2020 Aug 9;20(4):e31. Epub 2020 Jul 9.

Department of Pharmacy, Korea University College of Pharmacy, Sejong 30019, Korea.

The effectiveness of current influenza vaccines is considered suboptimal, and 1 way to improve the vaccines is using adjuvants. However, the current pool of adjuvants used in influenza vaccination is limited due to safety concerns. , or aloe, has been shown to have immunomodulatory functions and to be safe for oral intake. In this study, we explored the potential of orally administered processed gel (PAG) as an adjuvant for influenza vaccines in C57BL/6 mice. We first evaluated its adjuvanticity with a split-type pandemic H1N1 (pH1N1) Ag by subjecting the mice to lethal homologous influenza challenge. Oral PAG administration with the pH1N1 Ag increased survival rates in mice to levels similar to those of alum and MF59, which are currently used as adjuvants in influenza vaccine formulations. Similarly, oral PAG administration improved the survival of mice immunized with a commercial trivalent influenza vaccine against lethal homologous and heterologous virus challenge. PAG also increased hemagglutination inhibition and virus neutralization Ab titers against homologous and heterologous influenza strains following immunization with the split-type pH1N1 Ag or the commercial trivalent vaccine. Therefore, this study demonstrates that PAG may potentially be used as an adjuvant for influenza vaccines.
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http://dx.doi.org/10.4110/in.2020.20.e31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458799PMC
August 2020

Plausible Minimal Substrate for Erm Protein.

Antimicrob Agents Chemother 2020 08 20;64(9). Epub 2020 Aug 20.

Department of Bioscience and Biotechnology, The University of Suwon, Whasung City, Republic of Korea

Erm proteins methylate a specific adenine residue (A2058, coordinates) conferring macrolide-lincosamide-streptogramin B (MLS) antibiotic resistance on a variety of microorganisms, ranging from antibiotic producers to pathogens. To identify the minimal motif required to be recognized and methylated by the Erm protein, various RNA substrates from 23S rRNA were constructed, and the substrate activity of these constructs was studied using three Erm proteins, namely, ErmB from and ErmE and ErmS from The shortest motif of 15 nucleotides (nt) could be recognized and methylated by ErmS, consisting of A2051 to the methylatable adenine (A2058) and its base-pairing counterpart strand, presumably assuming a quite similar structure to that in 23S rRNA, an unpaired target adenine immediately followed by an irregular double-stranded RNA region. This observation confirms the ultimate end of each side in helix 73 for methylation, determined by the approaches described above, and could reveal the mechanism behind the binding, recognition, induced fit, methylation, and conformational change for product release in the minimal context of substrate, presumably with the help of structural determination of the protein-RNA complex. In the course of determining the minimal portion of substrate from domain V, protein-specific features could be observed among the Erm proteins in terms of the methylation of RNA substrate and cooperativity and/or allostery between the region in helix 73 furthest away from the target adenine and the large portion of domain V above the methylatable adenine.
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http://dx.doi.org/10.1128/AAC.00023-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449152PMC
August 2020

Development of functional composts using spent coffee grounds, poultry manure and biochar through microbial bioaugmentation.

J Environ Sci Health B 2017 Nov 21;52(11):802-811. Epub 2017 Sep 21.

d Department Environmental Engineering , Korea Maritime and Ocean University , Yeongdogu , Busan , South Korea.

Spent coffee grounds (SCG), poultry manure, and agricultural waste-derived biochar were used to manufacture functional composts through microbial bioaugmentation. The highest yield of tomato stalk-based biochar (40.7%) was obtained at 450°C with a surface area of 2.35 m g. Four pilot-scale composting reactors were established to perform composting for 45 days. The ratios of NH-N/NO-N, which served as an indicator of compost maturity, indicate rapid, and successful composting via microbial bioaugmentation and biochar amendment. Moreover, germination indices for radish also increased by 14-34% through augmentation and biochar amendment. Microbial diversity was also enhanced in the augmented and biochar-amended composts by 7.1-8.9%, where two species of Sphingobacteriaceae were dominant (29-43%). The scavenging activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH) were enhanced by 14.1% and 8.6% in the fruits of pepper plants grown in the presence of the TR-2 (augmentation applied only) and TR-3 (both augmentation and biochar amendment applied) composts, respectively. Total phenolic content was also enhanced by 68% in the fruits of the crops grown in TR-3. Moreover, the other compost, TR-L (augmentation applied only), boosted DPPH scavenging activity by 111% in leeks compared with commercial organic fertilizer, while TR-3 increased the phenolic content by 44.8%. Composting facilitated by microbial augmentation and biochar amendment shortened the composting time and enhanced the quality of the functional compost. These results indicate that functional compost has great potential to compete with commercially available organic fertilizers and that the novel composting technology could significantly contribute to the eco-friendly recycling of organic wastes such as spent coffee grounds, poultry manure, and agricultural wastes.
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http://dx.doi.org/10.1080/03601234.2017.1356165DOI Listing
November 2017

Overview of Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Patients with Type 2 Diabetes.

Am Health Drug Benefits 2017 Jun;10(4):178-188

Medical Director, Las Vegas Endocrinology, Clinical Associate Professor, Clinical Education, AZCOM, and Adjunct Associate Professor of Endocrinology, Touro University Nevada.

Background: It is estimated that 29.1 million people or 9.3% of the US population have diabetes, which contributes to considerable medical and financial burden. Type 2 diabetes mellitus is characterized by insulin resistance and insulin secretion impairment leading to hyperglycemia. The presence of insulin resistance is strongly correlated with obesity.

Objective: This article reviews the available glucagon-like peptide-1 (GLP-1) receptor agonists and their role in the management of patients with diabetes, to help guide the selection of the most suitable agent for the individualized treatment of patients with type 2 diabetes.

Discussion: This article reviews the evidence from phase 3 clinical trials for each of the 5 GLP-1 receptor agonists by comparing them against one another and with other existing therapies, including metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sulfonylureas. Incretin-based therapies have emerged as attractive agents for the treatment of type 2 diabetes. They target the GLP-1 hormone, which is partly responsible for insulin release and for attenuating hyperglycemia during meals (ie, the incretin effect). The 2 classes of incretin-based therapy currently available are GLP-1 receptor agonists and DPP-4 inhibitors, which prevent the breakdown of GLP-1. Both classes are attractive options, given their glucose-lowering effects without the adverse effects of hypoglycemia and weight gain. The different mechanisms of action of these therapies result in generally greater efficacy with GLP-1 receptor agonists, albeit at the expense of slightly increased gastrointestinal symptoms. These agents exert their effects by improving glucose-dependent insulin release, suppressing glucagon release, suppressing hepatic glucose output, and decreasing the rate of gastric emptying, thereby reducing appetite. Currently, 5 GLP-1 receptor agonists are available, including exenatide, liraglutide, albiglutide, dulaglutide, and lixisenatide; semaglutide may soon become available as the newest agent. With the exception of the investigational oral semaglutide, which has shown promising results, the other 5 agents are administered as subcutaneous injections, at different dosing intervals.

Conclusion: Currently, 5 GLP-1 receptor agonists are available for use in the United States. Although they are all in the same drug class, some significant differences exist among the various GLP-1 receptor agonists. The choice of a specific GLP-1 receptor agonist will depend on the patient preferences, potential adverse effects, and cost.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536194PMC
June 2017

From the Cover: Ethylmercury-Induced Oxidative and Endoplasmic Reticulum Stress-Mediated Autophagic Cell Death: Involvement of Autophagosome-Lysosome Fusion Arrest.

Toxicol Sci 2016 11 10;154(1):27-42. Epub 2016 Aug 10.

*School of Life Sciences and Biotechnology, Korea University, Seoul, Korea;

Ethylmercury (EtHg) is derived from the degradation of thimerosal, the most widely used organomercury compound. In this study, EtHg-induced toxicity and autophagy in the mouse kidney was observed and then the mechanism of toxicity was explored in vitro in HK-2 cells. Low doses of EtHg induced autophagy without causing any histopathological changes in mouse kidneys. However, mice treated with high doses of EtHg exhibited severe focal tubular cell necrosis of the proximal tubules with autophagy. EtHg dose-dependently increased the production of reactive oxygen species, reduced the mitochondrial membrane potential, activated the unfolded protein response, and increased cytosolic Calevels in HK-2 cells. Cell death induced by EtHg exposure was caused by autophagy and necrosis. N-acetyl cysteine and 4-phenylbutyric acid attenuated EtHg-induced stress and ameliorated the autophagic response in HK-2 cells. Furthermore, EtHg blocked autophagosome fusion with lysosomes, which was demonstrated via treatment with wortmannin and chloroquine. Low doses of EtHg and rapamycin, which resulted in minimal cytotoxicity, increased the levels of the autophagic SNARE complex STX17 (syntaxin 17)-VAMP8-SNAP29 without altering mRNA levels, but high dose of EtHg was cytotoxic. Inhibition of autophagic flux by chloroquin increased autophagosome formation and necrotic cell death in HK-2 cells. Collectively, our results show that EtHg induces autophagy via oxidative and ER stress and blockade of autophagic flux. Autophagy might play a dual role in EtHg-induced renal toxicity, being both protective following treatment with low doses of EtHg and detrimental following treatment with high doses.
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http://dx.doi.org/10.1093/toxsci/kfw155DOI Listing
November 2016

Prevention of azoxymethane/dextran sodium sulfate-induced mouse colon carcinogenesis by processed Aloe vera gel.

Int Immunopharmacol 2016 Nov 30;40:428-435. Epub 2016 Sep 30.

College of Pharmacy, Chungbuk National University, Cheongju 28644, South Korea. Electronic address:

The preventive effect of a processed Aloe vera gel (PAG) on colon carcinogenesis was examined using an azoxymethane (AOM)-initiated and dextran sodium sulfate (DSS)-promoted mouse colon carcinogenesis model. Oral administration of PAG (200, or 400mg/kg/day) significantly reduced the multiplicity of colonic adenomas and adenocarcinomas compared with the AOM/DSS only-treated mice. In the mice treated with 400mg/kg of PAG, adenoma and adenocarcinoma development was reduced to 80% and 60%, respectively, compared to 100% in the PAG-untreated AOM/DSS-treated mice. Western blot analysis using colon extracts showed that PAG reduced the activation of nuclear factor kappa B (NF-κB), resulting in the inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression. PAG appeared to inhibit the NF-κB activation through the activation of peroxisome proliferator-activated receptor gamma. PAG also inhibited the expression and phosphorylation of signal transducer and activator of transcription 3, which is known to connect inflammation and cancer. In addition, PAG inhibited cell cycle progression-inducing cellular factors, such as extracellular signal-regulated kinases 1/2, cyclin-dependent kinase 4, and cyclin D1. On the other hand, PAG increased the expression of Caudal-related homeobox transcription factor 2, which is known to be a tumor suppressor in colorectal cancer. These findings show that PAG suppresses colitis-related colon carcinogenesis by inhibiting both chronic inflammation and cell cycle progression in the colon.
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http://dx.doi.org/10.1016/j.intimp.2016.09.022DOI Listing
November 2016

Induction of mast cell degranulation by triterpenoidal saponins obtained from Cimicifugae rhizoma.

Immunopharmacol Immunotoxicol 2016 Oct 1;38(5):311-8. Epub 2016 Jul 1.

a School of Life Sciences and Biotechnology, Korea University , Seoul , Republic of Korea ;

Cimicifugae rhizoma has been widely used as a traditional herbal medicine to treat inflammation and menopausal symptoms. In this study, we found that some of the triterpenoidal saponins purified from the ethanol extract of Cimicifugae rhizoma dramatically induced histamine release. The structure-related induction of mast cell degranulation by them and the mechanism of action were determined. β-Hexosaminidase release in HMC-1 cells was increased in a concentration-dependent manner, with maximal 6.5- and 8.5-fold increases, by 200 μg/mL 24-epi-7,8-didehydrocimigenol-3-O-xyloside (comp 1) and cimigenol 3-O-beta-d-xyloside (comp 4) compared with those treated with phorbol 12-myristate 13-acetate and A23187 (PMACI), respectively. However, β-hexosaminidase release was not changed by 7,8-dihydrocimigenol (comp 3), or 23-OAc-shengmanol-3-O-xyloside (comp 7). These triterpenoidal saponins changed neither the intracellular Ca(2+ )level nor the activation of PKC, both of which play essential roles in histamine release. However, cromolyn and ketotifen, membrane stabilizers, effectively inhibited the β-hexosaminidase release induced by comp 1 or comp 4 by 39 and 45%, respectively. Collectively, xylose on the cimigenol-related backbone among triterpene glycosides isolated from Cimicifugae rhizoma may play an important role in activating mast cells and induction of degranulation partly via membrane destabilization of mast cells.
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http://dx.doi.org/10.1080/08923973.2016.1201101DOI Listing
October 2016

Physical and Antibacterial Properties of Gold-Poly(ethyl methacrylate) Nanocomposites Prepared by In-Situ Polymerization.

J Nanosci Nanotechnol 2015 Sep;15(9):7244-8

In this paper, the physical and antimicrobial properties of gold-poly(ethyl methacrylate) nanocomposites (Au-PEMA) are evaluated. Characterization of gold nanoparticles was carried out based on UV-Vis spectroscopy and transmission electron microscopy (TEM). The specimens were characterized by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), and field emission scanning electron microscope (FE-SEM). We identified the thermal stability of Au-PEMA nanocomposites and the inhibitory effect of live bacterial attachment of Au-PEMA nanocomposites against S. mutans was also evaluated.
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http://dx.doi.org/10.1166/jnn.2015.10574DOI Listing
September 2015

Diagnosis and treatment of patients with thyroid cancer.

Am Health Drug Benefits 2015 Feb;8(1):30-40

Endocrinologist, Scripps Green Hospital, San Diego, CA.

Background: Thyroid cancer is the most common malignancy of the endocrine system, representing 3.8% of all new cancer cases in the United States and is the ninth most common cancer overall. The American Cancer Society estimates that 62,450 people in the United States will be diagnosed with thyroid cancer in 2015, and 1950 deaths will result from the disease.

Objective: To review the current approach to the diagnosis and treatment of patients with thyroid cancer.

Discussion: Over the past 3 decades, there has been a dramatic increase in the number of people diagnosed with thyroid cancer, which may be attributable to the wide use of imaging studies, including ultrasounds, computed tomography, magnetic resonance imaging, and positron emission tomography scans that incidentally detect thyroid nodules. Thyroid cancer is divided into several main types, with papillary thyroid cancer being the most common. The treatment options for patients with thyroid cancer include the surgical removal of the entire thyroid gland (total thyroidectomy), radioactive iodine therapy, and molecular-targeted therapies with tyrosine kinase inhibitors. This article summarizes the diagnosis and treatment of thyroid cancer, with recommendations from the American Thyroid Association regarding thyroid nodules and differentiated thyroid cancer. Recently approved drugs and treatment trends are also explored.

Conclusion: The prognosis and treatment of thyroid cancer depend on the tumor type and its stage at the time of diagnosis. Many thyroid cancers remain stable, microscopic, and indolent. The increasing treatment options for patients with thyroid cancer, including therapies that were recently approved by the US Food and Drug Administration, have kept the mortality rate from this malignancy low, despite the increase in its incidence. Early diagnosis and appropriate treatment can improve prognosis and reduce mortality.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415174PMC
February 2015

Processed Aloe vera gel ameliorates cyclophosphamide-induced immunotoxicity.

Int J Mol Sci 2014 Oct 24;15(11):19342-54. Epub 2014 Oct 24.

College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.

The effects of processed Aloe vera gel (PAG) on cyclophosphamide (CP)-induced immunotoxicity were examined in mice. Intraperitoneal injection of CP significantly reduced the total number of lymphocytes and erythrocytes in the blood. Oral administration of PAG quickly restored CP-induced lymphopenia and erythropenia in a dose-dependent manner. The reversal of CP-induced hematotoxicity by PAG was mediated by the functional preservation of Peyer's patch cells. Peyer's patch cells isolated from CP-treated mice, which were administered PAG, produced higher levels of T helper 1 cytokines and colony-stimulating factors (CSF) in response to concanavalin A stimulation as compared with those isolated from CP-treated control mice. PAG-derived polysaccharides directly activated Peyer's patch cells isolated from normal mice to produce cytokines including interleukin (IL)-6, IL-12, interferon-γ, granulocyte-CSF, and granulocyte-macrophage-CSF. The cytokines produced by polysaccharide-stimulated Peyer's patch cells had potent proliferation-inducing activity on mouse bone marrow cells. In addition, oral administration of PAG restored IgA secretion in the intestine after CP treatment. These results indicated that PAG could be an effective immunomodulator and that it could prevent CP-induced immunotoxic side effects.
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http://dx.doi.org/10.3390/ijms151119342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264114PMC
October 2014

Estrogenic endocrine-disrupting chemicals modulate the production of inflammatory mediators and cell viability of lipopolysaccharide-stimulated macrophages.

Inflammation 2015 Apr;38(2):595-605

Department of Pharmacy, Korea University, Sejong, 339-700, Republic of Korea.

Estrogenic endocrine-disrupting chemicals (EDCs) are exogenous substances that act as competitive inhibitors of estrogen in the endocrine system. By disrupting the endocrine system, EDCs can cause severe disabilities and diseases, including cancers and altered sexual development. Although the influence of these molecules in the endocrine system is evident, the effects of EDCs on the immune system as well as their cytotoxicity have been poorly examined. Therefore, we selected 21 EDCs that are commonly found in Korean ecosystems, such as surface waters and effluents, and studied their immunologic effects by comparing nitric oxide (NO) production and cytotoxicity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (RAW cells), a macrophage cell line. Among the EDCs tested, fenitrothion (FTH) inhibited the messenger RNA (mRNA) expression of inducible NO synthase (iNOS), resulting in reduced NO production, while treatment with andostenedione (AD), diethyl phthalate, di-n-butyl phthalate (DBP), estriol, or molinate decreased production of NO in an iNOS-independent fashion. In contrast, benzo(a)pyrene (B(a)P) increased the production of NO in RAW cells. In addition, AD, DBP, or FTH inhibited the mRNA expression of tumor necrosis factor alpha or interleukin-1 beta. Treatment with 17-α-ethynylestradiol, 17-β-estradiol, 4-n-butyl phenol, or alachlor induced apoptosis of RAW cells, while dicyclohexyl phthalate and B(a)P caused cell death in an apoptosis-independent manner. These data suggest that EDCs can influence the immune response to pathogens by modulating the functions of macrophages.
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http://dx.doi.org/10.1007/s10753-014-9966-2DOI Listing
April 2015

Effects of a new sustained-release microsphere formulation of exenatide, DA-3091, on obese and non-alcoholic fatty liver disease mice.

Pharmazie 2013 Jan;68(1):58-62

College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.

The aim of this study was to examine the effects of a new sustained-release (SR) microsphere formulation of exenatide, DA-3091, on body weight gain and hepatic injury in high fat diet (HFD)-induced obese mice and high sucrose diet (HSD)-induced non-alcoholic fatty liver disease (NAFLD) mice. Then, we determined whether DA-3091 has the potency as a drug for the treatment of metabolic disease. In obese mice, after 8-week treatment, the body weight gain was significantly more suppressed by both 1 mg/kg and 2 mg/kg of DA-3091, monthly subcutaneous administered, than by 10 mg/kg/day of sibutramin, a drug against obesity. In NAFLD mice, a significant reduction in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, representative markers of hepatic injury, was observed after biweekly subcutaneous administration of 1 mg/kg and 2 mg/kg of DA-3091 for 8 weeks. A significant reduction in hepatic lipid accumulation was observed in DA-3091 treated groups as well. Based on these results, it is demonstrated that DA-3091 has the potency as a drug for the treatment of metabolic disease.
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January 2013

2,3,6-Trisubstituted quinoxaline derivative, a small molecule inhibitor of the Wnt/beta-catenin signaling pathway, suppresses cell proliferation and enhances radiosensitivity in A549/Wnt2 cells.

Biochem Biophys Res Commun 2013 Feb 21;431(4):746-52. Epub 2013 Jan 21.

School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.

GDK-100017, a 2,3,6-trisubstituted quinoxaline derivative, reduced β-catenin-T-cell factor/lymphoid enhancer factor (TCF/LEF)-dependent transcriptional activity and inhibited cell proliferation in a dose-dependent manner with an IC₅₀ value of about 10 μM in A549/Wnt2 cells. GDK-100017 down-regulated the expression of Wnt/β-catenin pathway target genes such as cyclin D1 and Dkk1 but not c-myc or survivin. GDK-100017 inhibited cell proliferation by arresting the cell cycle in the G1 phase not only in A549/wnt2 cells but also in SW480 colon cancer cells. In addition to its wnt signaling inhibitory properties, GDK-100017 also enhanced the radiosensitivity of the A549 human NSCLC line. These results suggest that GDK-100017 possesses potential anti-cancer activity by inhibiting the Wnt/β-catenin signal pathway, blocking the β-catenin-TCF/LEF interaction, and enhancing radiosensitivity.
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http://dx.doi.org/10.1016/j.bbrc.2013.01.038DOI Listing
February 2013

A tobacco CBL-interacting protein kinase homolog is involved in phosphorylation of the N-terminal domain of the cucumber mosaic virus polymerase 2a protein.

Biosci Biotechnol Biochem 2012 7;76(11):2101-6. Epub 2012 Nov 7.

College of Life Sciences and Biotechnology, Korea University, Anam-dong, Seoul 136-701, Korea.

The replication and transcription of cucumber mosaic virus (CMV) are catalyzed by multi-protein complex RNA-dependent RNA polymerase (RdRp), which is composed of the viral-encoded 1a and 2a proteins with host factors. We have reported that the N-terminal region of the polymerase 2a protein, composed of 126 amino acids, is required for interaction with the helicase 1a protein, and that the phosphorylation of the region abrogated interaction with the 1a protein, suggesting a mechanism of resistance in host plants against viral infection. Here, we found that three protein 2a kinases, of 60, 55, and 38 kDa, co-purified with the tobacco membrane fraction in an in-gel kinase assay. By yeast two-hybrid library screening using the N-terminal 126 amino acids of 2a as a bait, we identified CBL-interacting protein kinase 12 (NtCIPK12) corresponding to 55 kDa protein 2a kinase. The bacterially expressed protein kinase showed protein 2a kinase (t2aK) activity in vitro. We found that NtCIPK12 stabilized upon CMV infection at the post-translational level, and accumulated more heavily to the membrane than in the cytosol.
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http://dx.doi.org/10.1271/bbb.120474DOI Listing
May 2013

Comparability studies of new 3rd generation recombinant human factor VIII GreenGene F after improvement of formulation and viral inactivation/removal process.

Biologicals 2012 Nov 9;40(6):405-14. Epub 2012 Oct 9.

GC-Research Center, Green Cross Corporation, Yongin-city, South Korea.

A new 3rd generation recombinant factor VIII (rFVIII), GreenGene F (WHO INN: beroctocog alfa), which is a highly homogenous B-domain deleted FVIII protein comprising of two peptides as heavy chain (A1 and A2 domain) and light chain (A3, C1, and C2 domain) at 80 and 90 kDa, was developed from its predecessor product GreenGene (2nd generation product previously approved by Korea FDA after clinical studies in South Korea) by process improvements of i) addition of Solvent/Detergent treatment for virus inactivation, ii) nanofiltration (20 nm pore size) for viral removal and iii) alterations to an albumin-free formulation to minimize the risk of viral contamination. An assessment of comparability between the two products was made to see if process improvements for safer product manufacturing affected the rFVIII structural and functional characteristics. Physicochemical and physiological characteristics were observed, in vivo efficacy following a single intravenous administration to FVIII knock-out mice and toxicity by various GLP in vivo tests were evaluated. All results showed equivalence, proving that no changes in protein characteristics of rFVIII occurred from process changes in formulation, viral inactivation, and viral removal which minimize the risk of pathogen transmission to enhance safety.
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http://dx.doi.org/10.1016/j.biologicals.2012.09.004DOI Listing
November 2012

Mixture of three amino acids as stabilizers replacing albumin in lyophilization of new third generation recombinant factor VIII GreenGene F.

Biotechnol Prog 2012 Nov-Dec;28(6):1517-25. Epub 2012 Oct 23.

GC-Research Center, Green Cross Corporation, 341 Bojeong-dong, Giheung-gu, Yongin, Korea.

A formulation with stabilizers replacing albumin was developed for lyophilization of recombinant factor VIII (FVIII), GreenGene F (WHO INN: beroctocog alfa), to achieve stability and eliminate safety issues of blood-derived albumin. L-Arginine (hydrophilic amino acid, positively charged side chain), L-glutamic acid (hydrophilic amino acid, negatively charged side chain), and L-isoleucine (hydrophobic amino acid, nonpolar) were selected as stabilizers, and the mixture of the three amino acids were optimized. The mixture had results comparative with albumin and other commonly used stabilizers showing good preservation of recombinant FVIII during lyophilization, robust stability with consistently high recovery of FVIIII, very low aggregate formation, and good storage stability without alterations in protein characteristics. In vivo test results showed that the efficacy was maintained and had no signs of toxicity. The study demonstrated that the three amino acid mixture acts as a good stabilizer for lyophilization of recombinant FVIII and as a safe excipient.
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http://dx.doi.org/10.1002/btpr.1640DOI Listing
May 2013

Dietary Aloe QDM Complex Reduces Obesity-Induced Insulin Resistance and Adipogenesis in Obese Mice Fed a High-Fat Diet.

Immune Netw 2012 Jun 30;12(3):96-103. Epub 2012 Jun 30.

College of Pharmacy, SahmYook University, Seoul 139-742, Korea.

Obesity-induced disorders contribute to the development of metabolic diseases such as insulin resistance, fatty liver diseases, and type 2 diabetes (T2D). In this study, we evaluated whether the Aloe QDM complex could improve metabolic disorders related to blood glucose levels and insulin resistance. Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of Aloe QDM complex or pioglitazone (PGZ) or metformin (Met) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Dietary Aloe QDM complex lowered body weight, fasting blood glucose, plasma insulin, and leptin levels, and markedly reduced the impairment of glucose tolerance in obese mice. Also, Aloe QDM complex significantly enhanced plasma adiponectin levels and insulin sensitivity via AMPK activity in muscles. At the same time, Aloe QDM decreased the mRNA and protein of PPARγ/LXRα and scavenger receptors in white adipose tissue (WAT). Dietary Aloe QDM complex reduces obesity-induced glucose tolerance not only by suppressing PPARγ/LXRα but also by enhancing AMPK activity in the WAT and muscles, both of which are important peripheral tissues affecting insulin resistance. The Aloe QDM complex could be used as a nutritional intervention against T2D.
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http://dx.doi.org/10.4110/in.2012.12.3.96DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422715PMC
June 2012

Estrogenic/antiestrogenic activities of a Epimedium koreanum extract and its major components: in vitro and in vivo studies.

Food Chem Toxicol 2012 Aug 18;50(8):2751-9. Epub 2012 May 18.

School of Life Sciences & Biotechnology, Korea University, Seoul, Republic of Korea.

The estrogenic and antiestrogenic activities of Epimedii Herba, which is a traditional medicinal herb used in Korea and China were investigated in this study. The in vitro estrogen receptor (ER) mediated estrogenic/antiestrogenic activities of an Epimedii Herba extract (Epi ext) and its major components were determined using an estrogen responsive element driven reporter gene assay in MCF-7/ERE and HEK293T cells. The Epi ext exhibited ERα- and ERβ-mediated estrogenic activity with an EC(50) of 5.0 and 17.8 μM in HEK293T cells, respectively. Prenylflavonoid glycosides such as icariin (ICA), epimedin A, B, and C did not show any in vitro estrogenic or antiestrogenic activities. Icaritin (ICT) and quercetin exhibited in vitro ER mediated estrogenic activity with a more potent interaction with ERβ. In vivo estrogenic activities of the Epi ext, ICA and ICT were compared using an uterotrophic assay. Although the potency of in vitro estrogenic activity was in the order of ICT>Epi ext>ICA, ICA had the strongest estrogenic activity and next ICT in ovariectomized rats. These results collectively suggest that phytoestrogens possess both estrogenic and antiestrogenic activity, and that the differential expression of these two compounds with opposing activities is dependent on the physiological environment in terms of estrogen level, which may be the case in humans.
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http://dx.doi.org/10.1016/j.fct.2012.05.017DOI Listing
August 2012

Peripubertal administration of icariin and icaritin advances pubertal development in female rats.

Biomol Ther (Seoul) 2012 Mar;20(2):189-95

School of Life Sciences and Biotechnology, Korea University, Seoul 136-701.

Epimedii Herba is a traditional medicinal herb used in Korea and China and exerts estrogenic activity. In this study, we investigated the effect of peripubertal administration of Epimedii Herba on pubertal development in female rats using a modified protocol of the rodent 20-day pubertal female assay. Female Sprague-Dawley rats (21 days old after weaning, 10 rats per group) were divided into five groups: saline (Con), ethinyl estradiol (E2), Epimedii Herba ext (Ext), icariin (ICI), and icaritin (ICT), which were administered by oral gavage (E2 by subcutaneous injection) from postnatal day (PND) 21 through PND40. The time to vaginal opening (VO) was shorter for the Epimedii groups, particularly for the ICT group (p<0.05). Treatment with ICI and ICT significantly increased the duration of the estrus cycle (ICI, 2.78 days; ICT, 4.0 days; control, 1.78 days). Ovary weight was reduced by E2 treatment and increased by the Ext, ICI, and ICT treatments while the weight of the uterus and pituitary glands increased significantly only in the E2 and ICT groups. Although Epimedii Herba displayed relatively weak estrogenic activity, its repeated administration could affect pubertal development in female rats.
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http://dx.doi.org/10.4062/biomolther.2012.20.2.189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792217PMC
March 2012

Structural identification and biological activity of positional isomers of long-acting and mono-PEGylated recombinant human granulocyte colony-stimulating factor with trimeric-structured methoxy polyethylene glycol N-hydroxysuccinimidyl functional group.

Anal Biochem 2012 Apr 26;423(2):286-93. Epub 2011 Dec 26.

College of Life Sciences and Biotechnology, Korea University, Anam-dong, Seoungbuk-gu, Seoul 136-701, Republic of Korea.

The individual positional isomers from the mono-PEGylated recombinant human granulocyte colony-stimulating factor (rhG-CSF) were successfully isolated with additional strong cation exchange chromatography using Source 15S. The three isolated individual positional isomers were found to be homogeneous by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), analytical size exclusion high-performance liquid chromatography (SE-HPLC), and analytical cation exchange HPLC (CIE-HPLC) and were also characterized with respect to site of PEGylation by enzymatic digestion with endoproteinase Lys-C and N-terminal sequencing. In addition, in vitro biological activity was determined by cell proliferation assay. It was determined that the three isolated individual positional isomers were PEGylated at Lys35, Met(N-terminal), and Lys17 of the rhG-CSF molecule with a 23-kDa trimer-structured methoxy polyethylene glycol N-hydroxysuccinimidyl functional group (mPEG-NHS). All individual positional isomers (Lys35-PEGylated rhG-CSF, Met(N-terminal)-PEGylated rhG-CSF, and Lys17-PEGylated rhG-CSF) retained in vitro biological activity and were found to be 18.5%, 37.6%, and 7.1%, respectively, compared with the rhG-CSF molecule. The significantly different in vitro biological activities observed in the individual positional isomers could be presumably due to interference of receptor binding or active sites on the rhG-CSF molecule. In conclusion, the individual positional isomers isolated from the mono-PEGylated rhG-CSF were well characterized with respect to the site of PEGylation involving Lys35, Met(N-terminal), and Lys17. This characterization of the individual positional isomers would be critical to provide a basis for establishing consistency in the manufacturing process.
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http://dx.doi.org/10.1016/j.ab.2011.12.014DOI Listing
April 2012

Anti-inflammatory activity of 6-hydroxy-2,7-dimethoxy-1,4-henanthraquinone from tuberous roots of yam (Dioscorea batatas) through inhibition of prostaglandin D₂ and leukotriene C₄ production in mouse bone marrow-derived mast cells.

Arch Pharm Res 2011 Sep 6;34(9):1495-501. Epub 2011 Oct 6.

College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea.

6-Hydroxy-2,7-dimethoxy-1,4-phenanthraquinone (PAQ) isolated from the tuberous roots of Yam (Dioscorea batatas) inhibited cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) dependent prostaglandin D(2) (PGD(2)) generation in mouse bone marrow-derived mast cells in a concentration-dependent manner with IC(50) values of 0.08 μM and 0.27 μM, respectively. In the Western blotting with specific anti-COX-2 antibodies, the decrease of the quantity of PGD(2) was accompanied by a decrease in the COX-2 protein level. But PAQ did not affect COX-1 protein level. In addition, this compound inhibited 5-lipoxygenase (5-LOX) dependent production of leukotriene C(4) in a dose-dependent manner, with an IC(50) of 0.032 μM. These results demonstrate that PAQ has a dual COX-2/5-LOX inhibitory activity. This compound also inhibited the degranulation reaction in a dose-dependent manner with an IC(50) of 2.7 μM. Thus, these results suggest that PAQ may be useful in regulating mast cell-mediated inflammatory diseases.
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http://dx.doi.org/10.1007/s12272-011-0911-8DOI Listing
September 2011

Dietary Aloe Reduces Adipogenesis via the Activation of AMPK and Suppresses Obesity-related Inflammation in Obese Mice.

Immune Netw 2011 Apr 30;11(2):107-13. Epub 2011 Apr 30.

Department of Food and Nutrition, Seoul National University, Seoul 151-742, Korea.

Background: Metabolic disorders, including type II diabetes and obesity, present major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes. In this study, we evaluated whether dietary aloe could reduce obesity-induced inflammation and adipogenesis.

Methods: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation.

Results: Aloe QDM complex down-regulated fat size through suppressed expression of scavenger receptors on adipose tissue macrophages (ATMs) compared with HFD. Both white adipose tissue (WATs) and muscle exhibited increased AMPK activation through aloe supplementation, and in particular, the Aloe QDM complex. Obesity-induced inflammatory cytokines (IL-1β and -6) and HIF1α mRNA and protein were decreased markedly, as was macrophage infiltration by the Aloe QDM complex. Further, the Aloe QDM complex decreased the translocation of NF-κB p65 from the cytosol in the WAT.

Conclusion: Dietary aloe formula reduced obesity-induced inflammatory responses by activation of AMPK in muscle and suppression of proinflammatory cytokines in the WAT. Additionally, the expression of scavenger receptors in the ATM and activation of AMPK in WAT led to reduction in the percent of body fat. Thus, we suggest that the effect of the Aloe QDM complex in the WAT and muscle are related to activation of AMPK and its use as a nutritional intervention against T2D and obesity-related inflammation.
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http://dx.doi.org/10.4110/in.2011.11.2.107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100521PMC
April 2011

Dietary Aloe Improves Insulin Sensitivity via the Suppression of Obesity-induced Inflammation in Obese Mice.

Immune Netw 2011 Feb 28;11(1):59-67. Epub 2011 Feb 28.

Univera Inc., Seoul 133-120, Korea.

Background: Insulin resistance is an integral feature of metabolic syndromes, including obesity, hyperglycemia, and hyperlipidemia. In this study, we evaluated whether the aloe component could reduce obesity-induced inflammation and the occurrence of metabolic disorders such as blood glucose and insulin resistance.

Methods: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation.

Results: Aloe QDM lowered fasting blood glucose and plasma insulin compared with HFD. Obesity-induced inflammatory cytokine (IL-1β, -6, -12, TNF-α) and chemokine (CX3CL1, CCL5) mRNA and protein were decreased markedly, as was macrophage infiltration and hepatic triglycerides by Aloe QDM. At the same time, Aloe QDM decreased the mRNA and protein of PPARγ/LXRα and 11β-HSD1 both in the liver and WAT.

Conclusion: Dietary aloe formula reduces obesity-induced glucose tolerance not only by suppressing inflammatory responses but also by inducing anti-inflammatory cytokines in the WAT and liver, both of which are important peripheral tissues affecting insulin resistance. The effect of Aloe QDM complex in the WAT and liver are related to its dual action on PPARγ and 11β-HSD1 expression and its use as a nutritional intervention against T2D and obesity-related inflammation is suggested.
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http://dx.doi.org/10.4110/in.2011.11.1.59DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072676PMC
February 2011

Neuroprotective effects of Eucommia ulmoides Oliv. Bark on amyloid beta(25-35)-induced learning and memory impairments in mice.

Neurosci Lett 2011 Jan 23;487(1):123-7. Epub 2010 Oct 23.

Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.

In the present study, we examined whether aqueous extract of Eucommia ulmoides Oliv. Bark (EUE) with graded doses exerted its neuroprotective effects on amyloid beta(25-35) (Aβ(25-35))-induced learning and memory impairments in mice. Mice received a single intracerebroventricular (i.c.v.) injection of Aβ(25-35) 6 nmol as the critical factor in Alzheimer's disease (AD), cognition was evaluated using Y-maze, passive avoidance, and Morris water maze tests. EUE significantly improved the Aβ(25-35)-induced memory deficit in the Y-maze test. Also, EUE increased step-through latency time with Aβ(25-35)-induced learning and memory deficits in the passive avoidance test. In addition, EUE decreased the escape latencies with Aβ(25-35)-induced cognitive impairments in the Morris water maze test. In the probe trial session, EUE increased time spent in the target quadrant. In the in vitro study, EUE was found to inhibit acetylcholinesterase (AChE) activity in a dose-dependent manner (IC50 value; 172 μg/ml). Ex vivo study, EUE significantly inhibited AChE activity in the hippocampus and frontal cortex. These results demonstrate that EUE possesses potent neuroprotective effects and that its beneficial effects are mediated, in part, by AChE inhibition, and therefore, might be a potential candidate in neurodegenerative diseases such as AD.
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http://dx.doi.org/10.1016/j.neulet.2010.10.042DOI Listing
January 2011

Neuroprotective effects of chlorogenic acid on scopolamine-induced amnesia via anti-acetylcholinesterase and anti-oxidative activities in mice.

Eur J Pharmacol 2010 Dec 18;649(1-3):210-7. Epub 2010 Sep 18.

Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.

Chlorogenic acid is a major polyphenolic component of many plants and beverages, and is particularly abundant in coffee. We evaluated the neuroprotective effects of chlorogenic acid on learning and memory impairment induced by scopolamine (0.5 mg/kg, i.p.), a muscarinic antagonist, using the Y-maze, passive avoidance, and Morris water maze tests. The chlorogenic acid significantly improved the impairment of short-term or working memory induced by scopolamine in the Y-maze test, and significantly reversed cognitive impairments in mice as measured by the passive avoidance test. In addition, chlorogenic acid decreased escape latencies in the Morris water maze test. In a probe trial session, chlorogenic acid increased the latency time in the target quadrant in a dose-dependent manner. Ex vivo, chlorogenic acid inhibited acetylcholinesterase activity in the hippocampus and frontal cortex. Chlorogenic acid also decreased malondialdehyde levels in the hippocampus and frontal cortex. In vitro, chlorogenic acid was found to inhibit acetylcholinesterase activity (IC₅₀=98.17 μg/ml) and free radical scavenging activity (IC₅₀=3.09 μg/ml) in a dose-dependent manner. These results indicate that chlorogenic acid may exert anti-amnesic activity via inhibition of acetylcholinesterase and malondialdehyde in the hippocampus and frontal cortex.
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http://dx.doi.org/10.1016/j.ejphar.2010.09.001DOI Listing
December 2010

Identification of 2,3,6-trisubstituted quinoxaline derivatives as a Wnt2/β-catenin pathway inhibitor in non-small-cell lung cancer cell lines.

Bioorg Med Chem Lett 2010 Oct 29;20(19):5900-4. Epub 2010 Jul 29.

Graduate School of Biotechnology, Korea University, Seoul 136701, Republic of Korea.

We screened 1434 small heterocyclic molecules and identified thirteen 2,3,6-trisubstituted quinoxaline derivatives that were able to inhibit the Wnt/β-catenin signal pathway and cell proliferation. In the screen, some of the hit compounds such as the ethylene group-coupled quinoxaline derivatives were shown to hold promise for use as potential small-molecule inhibitors of the Wnt/β-catenin signal pathway in non-small-cell lung cancer cell lines.
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http://dx.doi.org/10.1016/j.bmcl.2010.07.088DOI Listing
October 2010

Anti-inflammatory activity of bark of Dioscorea batatas DECNE through the inhibition of iNOS and COX-2 expressions in RAW264.7 cells via NF-κB and ERK1/2 inactivation.

Food Chem Toxicol 2010 Nov 4;48(11):3073-9. Epub 2010 Aug 4.

College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.

We identified a bioactive herbal medicine with anti-inflammatory activity from an ethanol extract derived from the bark of Dioscorea batatas DECNE (BDB) in RAW264.7 cells. We examined the effects of BDB on nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in LPS-induced RAW264.7 cells. BDB consistently inhibited both NO and PGE(2) production in a dose-dependent manner, with an IC(50) of 87-71 μg/ml, respectively. The reduction of NO and PGE(2) production were accompanied by a reduction in iNOS and COX-2 protein expression, as evaluated by Western blotting. To evaluate the action mode of BDB and its ability to inhibit iNOS and COX-2 protein expression, we assessed the effects of BDB on nuclear factor-κB (NF-κB) DNA-binding activity, NF-κB-dependent reporter gene activity, inhibitory factor-κB (IκB) phosphorylation and degradation, and p65 nuclear translocation. BDB suppressed DNA-binding activity and reporter gene activity as well as translocation of the NF-κB p65 subunit. BDB also down-regulated IκB kinase (IKK), thus inhibiting LPS-induced both phosphorylation and the degradation of IκBα. In addition, BDB also inhibited the LPS-induced activation of ERK1/2.
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http://dx.doi.org/10.1016/j.fct.2010.07.048DOI Listing
November 2010

In vivo evidence of the immunomodulatory activity of orally administered Aloe vera gel.

Arch Pharm Res 2010 Mar 30;33(3):451-6. Epub 2010 Mar 30.

College of Pharmacy, Chungbuk National University, Cheongju, 361-763, Korea.

The gels of Aloe species contain immunomodulatory components such as aloctin A and acemannan. Most studies on these gels were performed in in vitro cell culture systems. Although several studies examined their immunomodulatory activity in vivo, the route of administration was intraperitoneal or intramuscular. Here, we evaluated the in vivo immunomodulatory activity of processed Aloe vera gel (PAG) in mice. Oral administration of PAG significantly reduced the growth of C. albicans in the spleen and kidney following intravenous injection of C. albicans in normal mice. PAG administration also reduced the growth of C. albicans in streptozotocin-induced diabetic mice. PAG administration did not increase ovalbumin (OVA)-specific cytotoxic T lymphocyte (CTL) generation in normal mice, but did increase it in high-fat-diet induced diabetic mice. These findings provide the first clear evidence for the immunomodulatory activity of orally administered Aloe vera gel.
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http://dx.doi.org/10.1007/s12272-010-0315-1DOI Listing
March 2010

Simultaneous determination of phenolic acids and phthalide compounds by liquid chromatography for quality assessment of Rhizoma cnidii.

J AOAC Int 2009 Mar-Apr;92(2):375-81

Korea Institute of Science and Technology, Doping Control Center, PO Box 131, Chungryang, Seoul 130-650, Korea.

This paper describes a simple, rapid, and validated reversed-phase high-performance liquid chromatographic method developed for the determination of 4 major bioactive constituents, namely, chlorogenic acid, ferulic acid, senkyunolide A, and Z-ligustilide in Rhizoma Cnidii extract. A Capcell Pak C18 chromatographic column (150 x 4.6 mm, 3 microm) was used with mobile phases consisting of 0.1% formic acid, acetonitrile, and methanol at a flow rate of 0.8 mL/min and UV detection at 285 nm. Comprehensive validation of the method included evaluation of linearity, repeatability, recovery, and stability. Excellent linear behavior (r2>0.99) was observed over the concentration range of 2-100 microg/mL for the compounds under investigation. Repeatability and accuracy were evaluated by intra- and interday assays; the relative standard deviation (RSD) values were < or = 5.37% and accuracies ranged from 97.1 to 104.9%. Recoveries of the compounds ranged from 94.2 to 104.2% with RSD values of < or = 9.50%. The developed method was successfully applied to the analysis of ethanolic extracts of Rhizoma Cnidii samples. As a result, the concentrations of chlorogenic acid, ferulic acid, Z-ligustilide, and senkyunolide A were determined to be 0.84-5.35, 0.45-1.65, 0.74-4.39, and 0.32-1.14 mg/g herb, respectively. Thus, the developed method was found to be accurate and reproducible and is considered suitable for the qualitative and quantitative analysis of Rhizoma Cnidii for bioactive compounds.
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July 2009

Hypoglycemic and hypolipidemic effects of processed Aloe vera gel in a mouse model of non-insulin-dependent diabetes mellitus.

Phytomedicine 2009 Sep 19;16(9):856-63. Epub 2009 Mar 19.

Department of Pharmacy, SahmYook University, Seoul, South Korea.

The effects of processed Aloe vera gel (PAG) on the course of established diet-induced non-insulin-dependent diabetes mellitus (NIDDM) were studied in C57BL/6J mice. NIDDM was induced in C57BL/6J mice by feeding them a high-fat diet. Mice exhibiting diet-induced obesity (DIO) with blood glucose levels above 180mg/dl were selected to examine the antidiabetic effects of PAG. Oral administration of PAG for 8 weeks reduced circulating blood glucose concentrations to a normal level in these DIO mice. In addition, the administration of PAG significantly decreased plasma insulin. The antidiabetic effects of PAG were also confirmed by intraperitoneal glucose tolerance testing. PAG appeared to lower blood glucose levels by decreasing insulin resistance. The administration of PAG also lowered triacylglyceride levels in liver and plasma. Histological examinations of periepididymal fat pad showed that PAG reduced the average size of adipocytes. These results demonstrate that the oral administration of PAG prevents the progression of NIDDM-related symptoms in high-fat diet-fed mice, and suggest that PAG could be useful for treating NIDDM.
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http://dx.doi.org/10.1016/j.phymed.2009.02.014DOI Listing
September 2009
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